title: Notch3 marks clonogenic mammary luminal progenitor cells in vivo.
abstract: The identity of mammary stem and progenitor cells remains poorly understood, mainly as a result of the lack of robust markers. The Notch signaling pathway has been implicated in mammary gland development as well as in tumorigenesis in this tissue. Elevated expression of the Notch3 receptor has been correlated to the highly aggressive "triple negative" human breast cancer. However, the specific cells expressing this Notch paralogue in the mammary gland remain unknown. Using a conditionally inducible Notch3-CreERT2(SAT) transgenic mouse, we genetically marked Notch3-expressing cells throughout mammary gland development and followed their lineage in vivo. We demonstrate that Notch3 is expressed in a highly clonogenic and transiently quiescent luminal progenitor population that gives rise to a ductal lineage. These cells are capable of surviving multiple successive pregnancies, suggesting a capacity to self-renew. Our results also uncover a role for the Notch3 receptor in restricting the proliferation and consequent clonal expansion of these cells.
authors.affiliation: Institut Curie, Centre de Recherche, 75248 Paris, Cedex 05, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lafkas
authors.forename: Veronica
authors.initials: V
authors.lastname: Rodilla
authors.forename: Mathilde
authors.initials: M
authors.lastname: Huyghe
authors.forename: Larissa
authors.initials: L
authors.lastname: Mourao
authors.forename: Hippokratis
authors.initials: H
authors.lastname: Kiaris
authors.forename: Silvia
authors.initials: S
authors.lastname: Fre
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D019070:Cell Lineage; D049109:Cell Proliferation; D002470:Cell Survival; D018920:Coculture Techniques; D061252:Feeder Cells; D005260:Female; D008321:Mammary Glands, Animal / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D041681:NIH 3T3 Cells; D011247:Pregnancy; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism*; D013997:Time Factors
chemical_list: D015415:Biomarkers; C499373:Notch3 protein, mouse; D000071656:Receptor, Notch3; D051880:Receptors, Notch